We have recently demonstrated that mammalian spermatozoa have the ability to degrade their DNA by a mechanism that is similar to apoptosis in somatic cells. When this mechanism is activated, the DNA is first degraded into loop-sized fragments by TOP2B (topoisomerase IIB). This degradation, termed sperm chromatin fragmentation, can be reversed by EDTA, which causes TOP2B to religate the double-stranded breaks it originally produced. Under certain conditions, a nuclease then degrades the sperm DNA further, digesting the entire sperm genome. When mouse spermatozoa which have been treated to induce TOP2B-mediated DNA breaks are injected into oocytes, the paternal DNA is specifically and completely degraded. This total digestion of paternal DNA occurs at the time of DNA synthesis initiation. In the present study, we explore the significance of an active TOP2B in the nucleus for mouse sperm function.